[GRG] Artificial Cells Produce Proteins and Communicate with Each Other

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Artificial Cells Act Like the Real Thing

18

Aug
2014

Materials Science

Cell-like compartments produce proteins and communicate with one
another, similar to natural biological systems

Imitation, they say, is the sincerest form of flattery, but
mimicking the intricate networks and dynamic interactions that are
inherent to living cells is difficult to achieve outside the cell.
Now, as published in Science, Weizmann Institute scientists have
created an artificial, network-like cell system that is capable of
reproducing the dynamic behavior of protein synthesis. This
achievement is not only likely to help gain a deeper understanding
of basic biological processes, but it may, in the future, pave the
way toward controlling the synthesis of both naturally-occurring
and synthetic proteins for a host of uses.

Eyal Karzbrun, Alexandra Tayar and Prof. Roy Bar-Ziv
(l-r) Eyal Karzbrun, Alexandra Tayar and Prof. Roy Bar-Ziv

The system, designed by PhD students Eyal Karzbrun and Alexandra
Tayar in the lab of Prof. Roy Bar-Ziv of the Weizmann Institute’s
Materials and Interfaces Department, in collaboration with Prof.
Vincent Noireaux of the University of Minnesota, comprises multiple
compartments “etched’’ onto a biochip. These compartments –
artificial cells, each a mere millionth of a meter in depth – are
connected via thin capillary tubes, creating a network that allows
the diffusion of biological substances throughout the system.
Within each compartment, the researchers insert a cell genome –
strands of DNA designed and controlled by the scientists
themselves. In order to translate the genes into proteins, the
scientists relinquished control to the bacterium E. coli: Filling
the compartments with E. coli cell extract – a solution containing
the entire bacterial protein-translating machinery, minus its DNA
code – the scientists were able to sit back and observe the protein
synthesis dynamics that emerged.

By coding two regulatory genes into the sequence, the scientists
created a protein synthesis rate that was periodic, spontaneously
switching from periods of being “on” to “off.” The amount of time
each period lasted was determined by the geometry of the
compartments. Such periodic behavior – a primitive version of cell
cycle events – emerged in the system because the synthesized
proteins could diffuse out of the compartment through the
capillaries, mimicking natural protein turnover behavior in living
cells. At the same time fresh nutrients were continuously
replenished, diffusing into the compartment and enabling the
protein synthesis reaction to continue indefinitely. “The
artificial cell system, in which we can control the genetic content
and protein dilution times, allows us to study the relation between
gene network design and the emerging protein dynamics. This is
quite difficult to do in a living system,” says Karzbrun. “The two-
gene pattern we designed is a simple example of a cell network, but
after proving the concept, we can now move forward to more
complicated gene networks. One goal is to eventually design DNA
content similar to a real genome that can be placed in the
compartments.”

artificial cells
Fluorescent image of DNA (white squares) patterned in circular
compartments connected by capillary tubes to the cell-free extract
flowing in the channel at bottom. Compartments are 100 micrometers
in diameter

The scientists then asked whether the artificial cells actually
communicate and interact with one another like real cells. Indeed,
they found that the synthesized proteins that diffused through the
array of interconnected compartments were able to regulate genes
and produce new proteins in compartments farther along the network.
In fact, this system resembles the initial stages of morphogenesis
– the biological process that governs the emergence of the body
plan in embryonic development. “We observed that when we place a
gene in a compartment at the edge of the array, it creates a
diminishing protein concentration gradient; other compartments
within the array can sense and respond to this gradient – similar
to how morphogen concentration gradients diffuse through the cells
and tissues of an embryo during early development. We are now
working to expand the system and to introduce gene networks that
will mimic pattern formation, such as the striped patterns that
appear during fly embryogenesis,” explains Tayar.

With the artificial cell system, according to Bar-Ziv, one can, in
principle, encode anything: “Genes are like Lego in which you can
mix and match various components to produce different outcomes; you
can take a regulatory element from E. coli that naturally controls
gene X, and produce a known protein; or you can take the same
regulatory element but connect it to gene Y instead to get
different functions that do not naturally occur in nature.” This
research may, in the future, help advance the synthesis of such
things as fuel, pharmaceuticals, chemicals and the production of
enzymes for industrial use, to name a few.

Prof. Roy Bar-Ziv’s research is supported by the Yeda-Sela Center
for Basic Research.

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About Johnny Adams

My full-time commitment is to slow and ultimately reverse age related functional decline to increase healthy years of life. I’ve been active in this area since the 1970s, steadily building skills and accomplishments. I have a good basic understanding of the science of aging, and have many skills that complement those of scientists so they can focus on science to advance our shared mission. Broad experience Top skills: administration, management, information technology (data and programming), communications, writing, marketing, market research and analysis, public speaking, forging ethical win-win outcomes among stakeholders (i.e. high level "selling"). Knowledge in grant writing, fundraising, finance. Like most skilled professionals, I’m best described as a guy who defines an end point, then figures out how to get there. I enjoy the conception, design, execution and successful completion of a grand plan. Executive Director Gerontology Research Group (GRG). Manages Email discussion forum, web site, meetings and oversees supercentenarian (oldest humans, 110+ years) research. CEO / Executive Director Carl I. Bourhenne Medical Research Foundation (Aging Intervention Foundation), an IRS approved 501(c)(3) nonprofit. http://www.AgingIntervention.org Early contributor to Supercentenarian Research Foundation. Co-Founder Geroscience Healthspan Forum. Active contributor to numerous initiatives to increase healthy years of life. Co-authored book on conventional, practical methods available today to slow the processes of aging – nutrition, exercise, behavior modification and motivation, stress reduction, proper supplementation, damage caused by improper programs, risk reduction and others. Fundamental understanding of, and experience in the genomics of longevity (internship analyzing and curating longevity gene papers). Biological and technical includes information technology, software development and computer programming, bioinformatics and protein informatics, online education, training programs, regulatory, clinical trials software, medical devices (CAT scanners and related), hospital electrical equipment testing program. Interpersonal skills – good communication, honest, well liked, works well in teams or alone. Real world experience collaborating in interdisciplinary teams in fast paced organizations. Uses technology to advance our shared mission. Education: MBA 1985 University of Southern California -- Deans List, Albert Quon Community Service Award (for volunteering with the American Longevity Association and helping an elderly lady every other week), George S. May Scholarship, CA State Fellowship. BA psychology, psychobiology emphasis 1983 California State University Fullerton Physiological courses as well as core courses (developmental, abnormal etc). UCLA Psychobiology 1978, one brief but fast moving and fulfilling quarter. Main interest was the electrochemical basis of consciousness. Also seminars at the NeuroPsychiatric Institute. Other: Ongoing conferences, meetings and continuing education. Aging, computer software and information technology. Some molecular biology, biotech, bio and protein informatics, computer aided drug design, clinical medical devices, electronics, HIPAA, fundraising through the Assoc. of Fundraising Professionals. Previous careers include: Marketing Increasing skill set and successes in virtually all phases, with valuable experience in locating people and companies with the greatest need and interest in a product or service, and sitting across the table with decision makers and working out agreements favorable to all. Information Technology: Management, data analysis and programming in commercial and clinical trials systems, and bioinformatics and protein informatics. As IT Director at Newport Beach, CA based technology organization Success Family of Continuing Education Companies, provided online software solutions for insurance and financial professionals in small to Fortune 500 size companies. We were successful with lean team organization (the slower moving competition was unable to create similar software systems). Medical devices: At Omnimedical in Paramount CA developed and managed quality assurance dept. and training depts. for engineers, physicians and technicians. Designed hospital equipment testing program for hospital services division. In my early 20’s I was a musician, and studied psychology and music. Interned with the intention of becoming a music therapist. These experiences helped develop valuable skills used today to advance our shared mission of creating aging solutions.
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